大豆苷元抗心律失常作用的研究

目的 :研究大豆苷元抗心律失常作用。方法 :常规抗心律失常方法。结果 :大豆苷元 (3.0,5.0mg·kg^-1)对氯仿诱发的小鼠室颤有明显的预防作用 ,大豆苷元 (0.8,1.0mg·kg^-1)对乌头碱诱发的大鼠心律失常有明显的治疗效果。大豆苷元 (0.2,0.3mg·kg^-1)还能对抗肾上腺素诱发的家兔心律失常 ,大豆苷元 (0.03% ,0.05%)能明显降低蟾蜍离体坐骨神经动作电位振幅。大豆苷元 (0.8,1.0mg·kg^-1)对氯化钙诱发的大鼠室颤具有预防作用 ,且能明显的降低大鼠的死亡率。以上作用具有明显的剂量依赖性。结论 :大豆苷元有明显的抗心律失常作用。其抗心律失常作用可能与其抑制Na⁺内流或Ca²⁺ 内流及与阻断-β 肾上腺素受体有关。     

Soy-based formulas and phyto-oestrogens: a safety profile

Phyto-oestrogens are non-steroidal plant-derived compounds that possess oestrogenic activity and act as selective oestrogen receptor modulators (SERMs). Among the dietary oestrogens, the isoflavone class enjoy a wide-spread distribution in most of the members of the Leguminosae family, including such prominent high-content representatives as soybean. Phyto-oestrogen research has grown rapidly in recent years owing to epidemiological studies suggesting that diets rich in soy may be associated with potential health benefits. There is a paucity of data on endocrine effects of soy phytochemicals during infancy, the most sensitive period of life for the induction of toxicity. The safety of isoflavones in infant formulas has been questioned recently owing to reports of possible hormonal effects. Infants fed soy formula receive high levels of phyto-oestrogens in the form of isoflavones (genistein, daidzein and their glycosides). To date, no adverse effects of short- or long-term use of soy proteins have been observed in humans and exposure to soy-based infant formulas does not appear to lead to different reproductive outcomes than exposure to cow milk formulas. Soy formula seems to be a safe feeding option for most infants. Nevertheless, much closer studies in experimental animals and human populations exposed to phyto-oestrogen-containing products, and particularly soy-based infant formulas, are necessary.     

大豆黄酮对卵巢切除大鼠鼻黏膜上皮细胞凋亡的保护作用

目的　观察双侧卵巢切除诱导大鼠鼻黏膜上皮细胞凋亡 ,研究尼尔雌醇、大豆黄酮对此的保护作用。方法　将 60只大鼠随机分为 4组 :健康对照组 ,卵巢切除组 ,卵巢切除 +尼尔雌醇组 ,卵巢切除 +大豆黄酮组。各组动物分期分 3批处死 ,流式细胞仪检测各组动物鼻中隔黏膜的早期凋亡细胞。结果　双侧卵巢切除后 ,大鼠鼻黏膜的早期凋亡细胞百分数增高 ,术后 60d达到新的平衡。大豆黄酮、尼尔雌醇干预组与健康组比较 ,早期凋亡细胞无明显改变。结论　雌激素替代和大豆黄酮可通过减少凋亡细胞而保护鼻黏膜免受雌激素缺乏的损害     

Modulation of Isoflavones on Bone—nodule Formation in Rat Calvaria Osteoblasts in vitro

Objective:to observe the effects of two main isoflavones,daidzein and genistein on the bone-nodule formation in rat calvaria osteoblasts in vitro.Methods:Osteoblasts obtained from newborn Sprague-dawley rat calvarias were cultured for several generations.The second generation cells were cultured in Minimum Essential Medium supplemenmted with ascorbic acid and Na-beta-glycerophosphate for several days,in the presence of daidzein and genistein,with or without the estrogen receptor antagonist ICI 182780.Number of nodules was counted at the end of the incubation period(day 20) by staining with Alizarin Red S calcium stain.The release of osteocalcin,as a marker of osteoblast activity,was also determined on day 7 and 12 during the incubation period.Results:compared with the control,the numbers of nodules were both increased by incubation with daidzin and genistein,17β-estradiol was used as a positive control and proved to be a more effective inducer of the increase in bone-nodules formation than daidzein and genisterin.The release of osteocalcin into culture media was also increased in the presence of daidzein and genistein,as well as 17β-estradiol on day 7 and day 12(day 12 were higher).The estrogen receptor antagonist ICI 182780 completely blocked the genistein-and 17β0estradiol-induced increase of nodule numbers and osteocalcin release in osteoblasts.Howerver,the effects induced by daidzein could not be inhibited by ICI 182780.Conclusion:These findings suggest that geinistein can stimulate bone-nodule formation and increase the release of osteocalcin in rat osteoblasts.The effects,like those induced by 17β-estradiol,are mediated by the estrogen receptor dependent pathway,Daidzin also can stimulate bone-nodule formation and increase the release of osteocalcin in rat osteoblasts,but it is not,at least not merely,mediated by the estrogen receptor dependent pathway.     

植物雌激素两种单体对子宫内膜腺上皮细胞作用的比较

目的 探讨植物雌激素两种单体在浓度5～80μmol／L对人子宫内膜腺上皮细胞增殖的影响。方法 2003年8～12月应用胶原酶阶梯消化法，原代培养人子宫内膜腺上皮细胞，用MTT方法观察植物雌激素的主要成分金雀黄素和大豆甙元对细胞体外增殖的影响。结果 低浓度的大豆甙元能促进子宫内膜腺上皮细胞轻度生长．随浓度的增加其作用明显，但当浓度达到40μmol／L，抑制细胞生长；不同浓度的金雀黄素均抑制子宫内膜腺上皮细胞的增殖。结论 植物雌激素两种单体对人子宫内膜腺上皮细胞的作用是明显不同的，提示在应用植物雌激素时要考虑不同成分的差别?     

Cyclodextrin encapsulation of daidzein and genistein by grinding: implication on the glycosaminoglycan accumulation in mucopolysaccharidosis type II and III fibroblasts

This work aimed to investigate the potential effect of cyclodextrin encapsulation on intrinsic ability of daidzein (DAD) and genistein (GEN) to inhibit the glycosaminoglycan (GAG) synthesis in fibroblasts originating from patients with mucopolysaccharidosis (MPS), type II and III. DAD or GEN encapsulation with either 2-hydroxypropyl-β-cyclodextrin or sulphobuthylether-β-cyclodextrin were achieved by neat grinding and were characterised by thermal analysis, X-ray powder diffraction, scanning electron microscopy and solubility testing which confirmed the complexes formation with increased solubility with respect to starting compounds. Both isoflavones, as well as their co-ground cyclodextrin complexes reduced GAG levels in the fibroblasts of MPS II and MPS III patients from 54.8–77.5%, in a dose dependent manner, without any significant cytotoxic effect. Cyclodextrin encapsulation did not change the intrinsically high effect of both DAD and GEN on the GAG level reduction in the treated cells, thus could be considered as a part of combination therapies of MPS.     

葛根素注射液治疗偏头痛急性发作临床观察

目的观察葛根素注射液对治疗偏头痛的影响,以进一步探讨葛根素注射液对偏头痛的治疗作用。方法研究组给予麦普宁注射液0.5 g+5%葡萄糖或0.85%生理盐水静点,1次/d;对照组给予低分子右旋糖苷500 mL静点,1次/d。共治疗20 d。结果葛根素治疗组与对照组在年龄、性别、偏头痛发作特点等之间均无显著差异,故在组间及治疗前有可比性。结论葛根素注射液对于偏头痛的治疗有较好疗效。     

Development of ELISAs for the measurement of the dietary phytoestrogens daidzein and equol in human plasma

Microtitration plate ELISAs were developed for the isoflavone daidzein, a phytoestrogen found mainly in soya and the mammalian metabolite of daidzein, equol. The detection limits in assay buffer were 21 pg per well for daidzein and 70 pg per well for equol. The assays were both highly specific. Human plasma was extracted with an organic solvent and standard curves for daidzein and equol were obtained in the presence of the extract. Applications of the assays are discussed.     

Reproductive safety studies with genistein in rats.

Genistein is a phytoestrogen that occurs naturally in the diet and is found in a wide variety of plant-derived foods especially in soybeans and soy-based foods. There is wide spread interest in genistein and related phytoestrogens as chemopreventive agents for a variety of human diseases and cancers based on epidemiologic evidence of reduced cancer rates in populations with a high intake of soy. Soy, and hence its constituents, such as genistein, have been consumed at high levels in several Asian populations for many centuries without any apparent adverse effects and to the contrary, many health benefits have been associated with the ingestion of soy based foods. Concern has been raised, however, of potential adverse effects due to the estrogenic and other activities of the isoflavones and thus a comprehensive series of safety studies was performed with genistein. To assess the teratogenic and fetal toxic potential of genistein, several studies were conducted. Genistein was tested in an in vitro rat whole embryo culture assay (WEC), which is a preliminary screen, for fetotoxic and teratogenic potential, over a concentration range of from 1 to 100 microg/mL. Treatment related anomalies were observed at concentrations of >or= 10 microg and at 100 microg/mL, all embryos were malformed. Two in vivo embryo fetal developmental safety studies were conducted with genistein by oral administration (gavage and dietary admix) in which there was no evidence for a teratogenic effect. In an oral (gavage) embryonic and fetal development pilot study, genistein was administered to rats at dose levels of 0, 20, 150 and 1000 mg/kg/day from days 6-20 of gestation to females that were allowed to litter and rear their offspring up to day 7 of lactation. A slight maternal toxicity at 1000 mg/kg/day was observed as indicated by decreased body weight and food consumption and at this dose, adverse effects in the pups were observed including increased pup mortality, poor general condition, reduced pup body weights, and reduced pup milk uptake. At the high dose of 1000 mg/kg, no external malformations were noted, however some minor visceral and skeletal variations were observed. At the low dose of 20 mg/kg/day, an increased mortality, reduced milk uptake, a decreased % male sex ratio, and decreased body weights during lactation were observed. Due to lack of effects at the mid dose and the small number of animals, a relationship to treatment was considered unlikely. In an oral (dietary admix) Prenatal developmental safety study, genistein was administered to rats at dose levels of 0, 5, 50, 100 and 500 mg/kg/day from day 5-21 of gestation. At 500 mg/kg, maternal body weight and food consumption were markedly reduced. The incidence of resorptions was markedly increased with a corresponding decrease in the number of live fetuses per dam. Fetal body weights were also reduced. No treatment-related teratogenic effects were noted during external, visceral and skeletal examination of fetuses or in body weight normalized anogenital distance. On the basis of these studies, it is concluded that genistein has no teratogenic potential in vivo at very high doses of up to 1000 mg/kg/day by oral gavage in the embryo-fetal toxicity pilot study or up to 500 mg/kg/day by dietary admix in the Prenatal developmental study even though these doses were maternally toxic and fetal-toxic. In vitro, genistein had teratogenic potential at high concentrations in the WEC screening assay, however this was not predictive of the in vivo findings. On the basis of the definitive Prenatal development study, the NOAEL for maternal toxicity and adverse effects on embryonic development was considered to be 100 mg/kg/day when administered orally by dietary admix.     

黄豆苷元半固体骨架型胶囊处方的初步研究

目的:采用半固体骨架技术提高黄豆苷元的体外溶出度。方法:采用熔融法制备黄豆苷元半固体骨架胶囊,比较不同载体材料聚氧乙烯(40)硬脂酸酯(S-40)、泊洛沙姆、聚乙二醇(PEG)4000,不同含药量(2%、4%、6%),表面活性剂吐温-80不同用量(15%、20%、25%、30%)对其体外溶出度的影响并与市售胶囊进行比较。结果:上述3种影响因素中溶出度较优的选择为采用S-40为载体,含药量为2%,吐温-80用量20%。所制胶囊体外溶出速率快于市售胶囊。结论:半固体骨架技术能够提高难溶性药物黄豆苷元的体外溶出度。